Phenylalanine (Phe) is an indispensable amino acid that is converted to tyrosine by the enzyme phenylalanine hydroxylase (PAH; EC 1.14.16.1) in an individual with normal metabolism. About 1 in every 15,000 infants born annually have absent or impaired function of this enzyme and are diagnosed with the metabolic disorder phenylketonuria (PKU) (Scriver C. R. 2001, The Metabolic & Molecular Bases of Inherited disease, 8th ed. New York: McGraw-Hill). If the diet of an individual with PKU is not modified within the first 20 days of life, Phe and its breakdown products accumulate in the blood and brain, causing neurological damage and cognitive disability.
Dietary management of PKU requires a low-Phe diet, suggested for life. Foods such as meat, dairy, legumes, and bread must be avoided by individuals with PKU because of the high Phe content. Although some low-protein natural foods are allowed in the low-Phe diet (mainly certain fruits and vegetables), the majority of dietary protein in the standard PKU diet is typically supplied by a Phe-free amino acid formula. A daily tally of total Phe consumption for adults older than 19 years of age must not exceed a target value from 220 to 770 mg/day for females or 290 to 1,200 mg/day for males (Acosta P & Yanicelli S. 2001, Protocol 1-Phenylketonuria (PKU), in Division, R. P., (editor), The Ross Metabolic Formula System Nutrition Support Protocols. 4th ed.: Ross Product Division).
The standard amino acid formula-based diet for PKU is difficult to follow, restrictive, and unpalatable. Non-compliance, a common problem with the standard PKU diet, can cause severe neuropsychological impairment. Thus, there is a need in the art for medical foods that are more palatable than the standard amino-acid based formulas and that provide PKU patients with necessary protein, including essential amino acids, while effectively maintaining low Phe levels in the blood and brain.